We are studying the cellular and molecular basis of autoimmune diseases with two purposes. First, we want to establish the pathogenic role and antigen-specificity of T cells that cause autoimmune diseases such as multiple sclerosis, myasthenia gravis, insulin-dependent diabetes, among others. Second, we would like to determine the feasibility of specific antigen-induced apoptosis as a means of treating such autoimmune diseases. To these ends, we have made progress in the following areas: 1) we have created a transgenic T cell receptor mouse model of myasthenia gravis which has a powerful response to a peptide from the acetylcholine receptor. 2) we have created transgenic mice that harbor an apoptosis inhibition gene in various immune cell lineages such as T cells, B cells,and dendritic cells to determine the risk to developing autoimmunity if apoptosis is inhibited in each of these lineages. 3) we have completed studies on the marmoset model of multiple sclerosis that indicate the usefulness of antigen-specific therapy. As part of these studies we are also trying to understand the regulation of antigen-induced death by T cell receptor stimulation. These studies should yield important new insights into the pathogenesis and treatment of autoimmune diseases which is a widespread health problem in the U.S. particularly among working women.